Biomedical subjects

B Zee

Publications and source records attributed to B Zee.

At least 19 recordsLinked to original sources

PubMed2007

A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity.

BACKGROUND: Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. This study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy. PATIENTS AND METHODS: Patients with early-stage breast or colon cancer who required postoperative adjuvant chemotherapy were eligible for the study. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version 2. RESULTS: One hundred and twenty patients were accrued at the time of premature study termination. Patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04). CONCLUSIONS: Traditional CHM does not reduce the hematologic toxicity associated with chemotherapy. CHM, however, does have a significant impact on control of nausea.

Adult↗

PubMed2006

Quality of life is predictive of survival in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients. MATERIALS AND METHODS: Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis. RESULTS: Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. CONCLUSIONS: In the studied HCC population, patient-reported baseline QoL provides additional prognostic information that supplements traditional clinical factors, and is a new prognostic marker for survival for patients with unresectable HCC.

Adolescent↗

PubMed2006

Role of laboratory variables in differentiating SARS-coronavirus from other causes of community-acquired pneumonia within the first 72 h of hospitalization.

The Centers for Disease Control and Prevention (CDC) recommend that SARS-coronavirus (SARS-CoV) testing be considered in epidemiologically high-risk patients hospitalized with community-acquired pneumonia (CAP) if no alternative diagnosis is identified after 72 h. The aim of this study was to identify routine laboratory variables that might indicate the need for SARS-CoV testing. Routine hematological/biochemical variables in patients with laboratory-confirmed SARS (2003) were compared with those in consecutive patients hospitalized June-December 2004 with radiologically confirmed CAP. Stepwise logistic regression analyses were performed to identify discriminating variables at baseline and by day 3 of hospitalization. Nasopharyngeal aspiration and antigen detection for influenza virus and respiratory syncytial virus using an immunofluorescence assay (IFA) were routinely performed in patients with CAP. Altogether, 181 patients with CAP (who remained undiagnosed by IFA) and 303 patients with SARS were studied. The mean intervals from symptom onset to admission were 3.1 and 2.8 days, respectively (p > 0.05). The etiological agent of CAP was identified retrospectively in only 39% of cases, the majority being bacterial pathogens. At baseline, age and absolute neutrophil count (ANC) were the only independent discriminating variables (p < 0.0001). Using a value of <4.4 x 10(9)/l as the cutoff for ANC, the sensitivity and specificity of ANC for discriminating SARS were 64 and 95%, respectively (AUC 0.90). By day 3 of hospitalization, age (p < 0.0001), change in ANC (p = 0.0003), and change in bilirubin (p = 0.0065) were discriminating variables. A model combining age <65 years, a change in ANC of >-3 x 10(9)/l, and a change in bilirubin of > or =0 mmol/l had a sensitivity of 43% and a specificity of 95% for SARS (AUC 0.90). There are only a few laboratory features (including lymphopenia) that clearly discriminate SARS from other causes of CAP. Nevertheless, when evaluating epidemiologically high-risk patients with CAP and no immediate alternative diagnosis, a low ANC on presentation along with poor clinical and laboratory responses after 72 h of antibiotic treatment may raise the index of suspicion for SARS and indicate a need to perform SARS-CoV testing.

Aged↗

PubMed2004

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy.

For cancer patients with chronic hepatitis B virus (HBV) infection, who receive cytotoxic chemotherapy, HBV reactivation is a well-described complication, which may result in varying degrees of liver damage. Several clinical features and the pre-chemotherapy HBV viral load have been suggested to be associated with an increased risk of developing the condition: (1). to assess the clinical and virological factors in a comprehensive manner and thereby identify those that are associated with the development of HBV reactivation; (2). to develop a predictive model to quantify the risk of HBV reactivation. In all, 138 consecutive cancer patients who were HBV carriers and undergoing chemotherapy were studied, of which 128 patients had sera available for real-time PCR HBV DNA measurement. They were followed up throughout their course of chemotherapy and the HBV reactivation rate was determined. The clinical and virological features between those who did and did not develop viral reactivation were compared. These included age, sex, baseline liver function tests, HBeAg status and viral load (HBV DNA) prior to the chemotherapy, and the use of specific cytotoxic agents. In all, 36 (26%) developed HBV reactivation. Multivariate analysis revealed pre-chemotherapy HBV DNA level, the use of steroids and a diagnosis of lymphoma or breast cancer to be significant factors. Based on real-time HBV DNA PCR assay, detectable baseline HBV DNA prior to the administration of cytotoxic chemotherapy, the use of steroids and a diagnosis of lymphoma or breast cancer are predictive factors for the development of HBV reactivation. A predictive model was developed from the current data, based on a logistic regression method.

Adult↗

PubMed2004

High hepatitis B virus (HBV) DNA viral load is an important risk factor for HBV reactivation in breast cancer patients undergoing cytotoxic chemotherapy.

Hepatitis B virus (HBV) reactivation during cytotoxic chemotherapy for cancer may complicate treatment and cause liver damage. The complication has been reported to occur in 10% to over 50% of HBV carriers, but the factors that determine which patients will develop reactivation remain unclear. The objective of the study is to test the hypothesis that the prechemotherapy HBV DNA level is a risk factor for the development of HBV reactivation. We studied 41 women undergoing cytotoxic chemotherapy for breast cancer, 17 of whom developed reactivation and 24 who did not. We developed a novel, ultra-sensitive, real-time polymerase chain reaction assay for the measurement of HBV DNA. The sera of 37 patients (16 who developed reactivation and 21 who did not) were available for measurement of HBV DNA using this technique. The results showed that patients in the reactivation group had a significantly higher median HBV DNA load (1.03 x 10(6) copies/mL; range <2.9 x 10(3) to 8.723 x 10(7)) than did the nonreactivation group (<2.9 x 10(3) copies/ml; range <2.9 x 10(3) to 6.331 x 10(7)) (P < 0.001). The optimal cut-off between the two groups was found to be at serum HBV DNA level of 3 x 10(5), which gave a sensitivity of 81.0% and a specificity of 85.0%. In conclusion, for breast cancer patients receiving standard cytotoxic chemotherapy, a high HBV viral load prior to the administration of cytotoxic chemotherapy is a significant predictive factor for the development of HBV reactivation. Such information may be useful in determining which patients would benefit most from prophylactic antiviral therapy during cytotoxic chemotherapy.

Antineoplastic Agents↗

PubMed2004

Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy.

BACKGROUND: Cancer patients who are hepatitis B virus (HBV) carriers and undergoing chemotherapy (CT) may be complicated by HBV reactivation. Over 80% of hepatocellular carcinoma (HCC) patients are HBV carriers; however, the incidence of HBV reactivation during CT has not been well-reported. A prospective study was conducted to determine the incidence of HBV reactivation, the associated morbidity and mortality, and possible risk factors. PATIENTS AND METHODS: 102 HBsAg-positive patients with inoperable HCC underwent systemic CT. Patients received either combination cisplatin, interferon, doxorubicin and fluorouracil (PIAF) or single-agent doxorubicin. They were followed up during and for 8 weeks after CT. RESULTS: In 102 patients, 59 (58%) developed hepatitis amongst whom 37 (36%) were attributable to HBV reactivation. Twelve (30%) died of HBV reactivation. CT was interrupted in 32 patients (86%) with reactivation and 54 (83%) without reactivation (P>0.05). The median survivals were 6.00 and 5.62 months, respectively (P=0.694). Elevated baseline alanine aminotransferase (ALT) was found to be a risk factor. CONCLUSION: HBV reactivation is a common cause of liver damage during CT in HBsAg-positive HCC patients. The only identifiable associated risk factor was elevated pre-treatment ALT. Further studies into the role of antiviral and novel anticancer therapies are required to improve the prognosis of these patients.

Adult↗

PubMed2003

Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To compare the selective matrix metalloproteinase inhibitor BAY 12-9566 with the nucleoside analog gemcitabine in the treatment of advanced pancreatic cancer. METHODS: Patients with advanced pancreatic adenocarcinoma who had not previously received chemotherapy were randomly assigned to receive BAY 12-9566 800 mg orally bid continuously or gemcitabine 1,000 mg/m2 administered intravenously on days 1, 8, 15, 22, 29, 36, and 43 for the first 8 weeks, and then days 1, 8, and 15 of each subsequent 28-day cycle. The primary end point was overall survival; secondary end points were progression-free survival, tumor response, quality of life, and clinical benefit. The planned sample size of the study was 350 patients. Two formal interim analyses were planned. RESULTS: The study was closed to accrual after the second interim analysis on the basis of the recommendation of the National Cancer Institute of Canada Clinical Trials Group Data Safety Monitoring Committee. There were 277 patients enrolled onto the study, 138 in the BAY 12-9566 arm and 139 in the gemcitabine arm. The rates of serious toxicity were low in both arms. The median survival for the BAY 12-9566 arm and the gemcitabine arm was 3.74 months and 6.59 months, respectively (P <.001; stratified log-rank test). The median progression-free survival for the BAY 12-9566 and gemcitabine arms was 1.68 and 3.5 months, respectively (P <.001). Quality-of-life analysis also favored gemcitabine. CONCLUSION: Gemcitabine is significantly superior to BAY 12-9566 in advanced pancreatic cancer.

Adenocarcinoma↗

PubMed2002

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.

Adult↗

PubMed2002

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Adult↗

PubMed2002

A randomized phase II study of two schedules of bryostatin-1 (NSC339555) in patients with advanced malignant melanoma: A National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: This study addressed the efficacy and toxicity of the novel compound Bryostatin-1 (NSC 339555), a novel agent with antineoplastic, hematopoietic and immunomodulatory activity in a variety of in vitro and in vivo systems. PATIENTS AND METHODS: This phase II study randomly assigned chemotherapy-naïve patients with untreated metastatic melanoma and measurable disease to two schedules of treatment: Arm A, 25 microg/m2 bryostatin-1 given as a 24 hour continuous infusion weekly or Arm B, 120 microg/m2 bryostatin-1 given as a 72 hour continuous infusion every 2 weeks. Although objective response was assessed using standard NCIC CTG criteria, antitumour activity was assessed using a multivariate endpoint incorporating both response (CR and PR) and early progression (PD at < or = 8 weeks). Seventeen patients were randomized to each arm. RESULTS: Arm A was better tolerated with 86.7% of 15 evaluable patients receiving > or = 90% of planned dose intensity versus 76.5% of 17 evaluable patients in Arm B. On Arm B, three patients experienced serious adverse events and three patients had to be removed from protocol therapy due to toxicity. The most common side effect was myalgia (33% grade 1-2 on Arm A versus 65% on Arm B with 5 patients experiencing grade 3 and one patient grade 4). Lethargy was more common on Arm A but more severe on Arm B. Other side effects such as nausea, diarrhea and headache were generally mild to moderate in nature and occurred with a similar frequency on both arms. Hematologic and biochemical toxicity were minimal. This trial was closed early because the protocol-stopping rule was met based on lack of required responses and on the number of early progressions on both arms. No partial or complete responses were seen; 3 patients randomized to Arm A had stable disease (duration 9-24 weeks) as did 4 patients (duration 10-38 weeks) randomized to Arm B. CONCLUSION: Arm A was better tolerated than Arm B. We conclude that bryostatin-1 has little efficacy in the treatment of metastatic melanoma with either of the schedules studied.

Adult↗

PubMed2001

Application of a new multinomial phase II stopping rule using response and early progression.

PURPOSE: A multinomial stopping rule had previously been developed that incorporated both objective response and early progression into decisions to stop or continue phase II trials of anticancer agents. The purpose of this study was to apply the multinomial rule to two independent sets of phase II data to assess its utility in appropriately recommending early trial closure as compared with other stopping rules. MATERIALS AND METHODS: Data from completed phase II trials of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and European Organization for Research and Treatment of Cancer Early Clinical Studies Group (ECSG) formed the basis of the study. Based on observed results for each trial, the recommendation of the multinomial stopping rule was applied, as was the recommendation of the actual stopping rule used (Fleming or Gehan). The appropriateness of the recommendations was evaluated based on interpretation of final study results. RESULTS: The standard and multinomial rules disagreed on early stopping in one of 16 NCIC CTG trials and in seven of 23 ECSG trials. In all cases, the standard rule advised continuing to the second stage whereas the multinomial rule advised stopping early because of excessive numbers of patients experiencing early disease progression. Final trial results indicated that the multinomial recommendation was appropriate, because in no study did final results lead to conclusions of activity. CONCLUSION: In this series of trials, the multinomial stopping rule performed more efficiently than the Fleming or Gehan rules in advising early stopping of trials. These results encourage continued exploration of this approach for phase II trials of cytotoxic and noncytotoxic anticancer agents.

Clinical Trials, Phase II as Topic↗

PubMed2001

Application of classification tree and neural network algorithms to the identification of serological liver marker profiles for the diagnosis of hepatocellular carcinoma.

OBJECTIVE: Although many attempts have been made to identify tumour-specific alpha-fetoprotein (AFP) glycoforms or other serological markers for the diagnosis of hepatocellular carcinoma (HCC), none of the available markers has, so far, shown satisfactory sensitivity and specificity. Here we aimed to apply classification tree and neural network algorithms to interpret the levels of multiple serological liver markers to improve overall specificity and sensitivity, particularly with a view to discriminating between liver cirrhosis with and without HCC. METHODS: We developed classification trees and neural networks that identified serological liver marker profiles comprising AFP, alpha1-antitrypsin (A1AT), alpha2-macroglobulin (A2MG), thyroxine-binding globulin (TBG), transferrin and albumin as well as sex and age, which might permit the diagnosis of HCC. Data were collected from 65 HCC patients, 51 patients with liver cirrhosis alone (LC) and 51 normal healthy subjects. RESULTS: The generated classification trees and neural networks showed similar diagnostic values in differentiating HCC from LC. The classification trees identified AFP, A1AT and albumin as the most important classification parameters, whereas the neural networks identified A2MG, AFP, A1AT and albumin as the predominant factors. The classification logic of the classification trees indicated that more HCC cases could be identified among cases with slightly elevated AFP levels by using the serum levels of A1AT and albumin. The neural networks were also useful for the identification of the HCC cases when the AFP levels were below 500 ng/ml (p < 0.005). The neural networks could identify HCC cases with AFP levels within the normal range, but the classification trees could not. By combining the conventional AFP test and the neural networks, the overall diagnostic sensitivity for HCC was significantly increased from 60.0 to 73.8% (p < 0.05) while maintaining a high specificity (88.2%). The sensitivities for tumors of different sizes were similar. CONCLUSION: The neural network algorithm appeared to be more powerful than the classification tree algorithm in the identification of the distinctive serological liver marker profiles for the diagnosis of the HCC subgroup without significant elevation in serum AFP levels. By incorporating serological levels of other liver markers and including data from a large number of patients and control subjects, it should prove possible to develop a versatile neural network for early diagnosis of HCC.

Adult↗

PubMed2000

A phase II study of gemcitabine plus oral etoposide in the treatment of patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The authors have designed a non-cisplatin-based chemotherapy regimen for the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). This regimen capitalizes on the mild toxicity of gemcitabine, a novel nucleoside analog. METHODS: A total of 46 chemotherapy-naive patients with histologically confirmed Stage IIIB or IV NSCLC were enrolled. Eligible patients were treated with gemcitabine 1000 mg/m(2) on Days 1, 8, and 15, plus oral etoposide 50 mg daily for 14 days, which was increased to 21 days if there was no World Health Organization (WHO) Grade 3 or 4 toxicity in the 1st 2 cycles (each cycle was 28 days long). All patients were included for analysis of response and survival according to an intention-to-treat principle. RESULTS: The overall response rate was 43.5% (95% confidence interval [CI], 30. 7-60.2%). There was 1 complete response (2.2%) and 19 partial responses (41.3%). The median survival was 48.0 weeks (95% CI, 38. 1-75.9 weeks) and the 1-year survival rate was 45% (95% CI, 29-62%). The median time to progression for all patients was 39.2 weeks (95% CI, 35.7-49.7 weeks). World Health Organization (WHO) Grade 3 and 4 anemia, neutropenia, and thrombocytopenia was reported in 29%, 32%, and 18% of patients, respectively. Two patients had reactivation of hepatitis B viral infection that resulted in WHO Grade 4 hepatic dysfunction. Other nonhematologic toxicities were uncommon. CONCLUSIONS: This non-cisplatin-based regimen of gemcitabine and oral etoposide achieved a high response and survival rate. Toxicity appeared to be less severe than that associated with existing cisplatin-based regimens. A randomized study of this regimen versus a cisplatin-based regimen is indicated.

Adult↗

PubMed2000

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Adult↗

PubMed2000

Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose.

PURPOSE: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All T1 and T2 (nasal infiltration) NPC treated with a curative intent from 1984 to 1996 were analyzed (n = 509). One hundred sixty-three patients were given ICT after radical external radiotherapy (ERT) (Group A). They were compared with 346 patients treated by ERT alone (Group B). The ERT delivered the tumoricidal dose (uncorrected BED-10 > or =75 Gy) to the primary tumor and did not differ between the two groups in technique or dosage. The ICT delivered a dose of 18-24 Gy in 3 fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. ICT was used to treat local persistence diagnosed at 4-6 weeks after ERT (n = 101) or as an adjuvant for the complete responders to ERT (n = 62). RESULTS: The two groups did not differ in patients' age or sex, rate of distant metastasis, rate of regional failure, overall survival, or the follow-up duration. However, Group A had significantly more T2 lesions and Group B had significantly more advanced N-stages. Local failure was significantly less (crude rates 6.75% vs. 13.0%; 5-year actuarial rates 5.40% vs. 10.3%) and the disease-specific mortality was significantly lower (crude rates 14.1% vs. 21.7%; 5-year actuarial rates 11.9% vs. 16.4%) in Group A compared to Group B. Multivariate analysis showed that the ICT was the only significant prognostic factor predictive for fewer local failures (Cox regression p = 0.0328, risk ratio = 0.49, 95% confidence interval (95% CI) = 0.256-0.957). However, when ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumor repopulation during the period of radiotherapy became significant in predicting ultimate local failure rate. The two groups were comparable in the incidence rates of each individual chronic radiation complication and the actuarial cumulative rate of the chronic radiation complications, with the exception of chronic radiation nasopharyngeal ulceration/necrosis which occurred in 10 patients in Group A and 1 patient in Group B. Headache (n = 4) and foul smell (n = 8) consequential to ulceration/necrosis were mild and manageable by conservative means. A significant dose-tumor-control relationship existed when local failure was studied as a function of the total physical dose or the total biological equivalent dose (linear quadratic equation, alpha/beta = 10) uncorrected for tumor repopulation during the time course of the radiotherapy. CONCLUSIONS: Supplementing ERT which delivered tumoricidal dose (uncorrected BED-10 > or =75 Gy), ICT significantly enhanced ultimate local control and avoided the necessity for morbid salvage treatments in early T-stage (T1/T2 nasal infiltration) NPC. The slight increase in chronic radiation ulceration/necrosis after ICT was acceptable with mild and manageable symptoms. Other late complications were not increased. A significant dose-tumor-control relationship exists above the conventional tumoricidal dose level.

Adult↗

PubMed2000

Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors.

Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12-month period. Seventy-eight patients (12%) were found to be HBsAg positive. Thirty-four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre-treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV-related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation.

Adult↗

PubMed2000

Improved local control for early T-stage nasopharyngeal carcinoma--a tale of two hospitals.

PURPOSE: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All early T-stage (T1 and T2 nasal cavity tumour) NPC treated with a curative intent up to 1996 were analyzed (n=743), 163 from the Prince of Wales Hospital (PWH) and 25 from Tuen Mun Hospital (TMH) were given ICT after radical external radiotherapy (ERT; group A). They were compared with 555 patients treated with ERT alone (group B). The radiotherapy techniques were identical between the two hospitals. The ERT delivered the tumoricidal dose (uncorrected biological equivalent dose (BED)-10, > or = 75 Gy) to the primary tumour, and this did not differ in technique or dosage between the two groups. The ICT delivered a dose of 18-24 Gy in three fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. RESULTS: The local failure was significantly less (crude rates, 6.9 vs. 13.0%; 5-year actuarial rates, 5.8 vs. 11.7%) and the disease-specific mortality was significantly lower (crude rates, 13.8 vs. 18.9%; 5-year actuarial rates, 12.2 vs. 15.2%) in group A compared with group B. ICT was the only significant independent prognostic factor predictive of fewer local failures. When ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumour repopulation became significant in predicting the ultimate local failure rate. The two groups were comparable in the rate of the chronic radiation complications. A significant dose-tumour-control relationship existed, plotting the local failure as a function of the total physical dose or the total BED. CONCLUSIONS: Supplementing ERT, which delivered the tumoricidal dose (uncorrected BED-10, > or = 75 Gy), with ICT significantly enhanced ultimate local control in early T-stage (T1/T2 nasal infiltration) NPC. A significant dose-tumour-control relationship exists above the conventional tumoricidal dose level.

Adult↗

PubMed2000

Mammographic density changes in perimenopausal and postmenopausal women: is effect of hormone replacement therapy predictable?

BACKGROUND: Mammographic density adversely affects diagnostic accuracy and may be a risk factor for breast cancer. Mammographic density is affected by hormone replacement therapy (HRT). OBJECTIVE: To assess mammographic density in postmenopausal women with and without HRT. METHOD: Part I. Mammographic density was determined in 1232 postmenopausal women attending a breast screening clinic. Density was compared between HRT users and nonusers in three age groups. When available, previous mammograms were assessed for interval density change. Part II. Density change in 162 women during transition from premenopause to postmenopause was recorded. HRT effect was assessed. RESULTS: Part I. There was no density difference between postmenopausal HRT-users and nonusers younger than age 55. Thereafter, the density was significantly less in nonusers. In the majority of HRT-users the density remained at pretreatment levels but density increased in 8% of women after HRT was started. Part II. Of 117 HRT nonusers followed over menopause 38% had a density decrease before age 55. Of those started on HRT, 80% had no density change, 18% decreased density and 2% increased density. CONCLUSIONS: The density decreases significantly after age 55 with the greatest change occurring between age 55 and 64. This decrease does not occur in the majority of HRT-users. Usually HRT maintains the density present at the time HRT is started. Density decreases after HRT is started in some women suggesting refractoriness to hormones. In fewer than 8% of women density increases commensurate with HRT. Any adverse effect of HRT may depend on the receptivity of the epithelial elements which, in turn, may be reflected by the mammographic density at the time HRT is started.

Adult↗